The role of short chain fatty acids in appetite regulation and energy homeostasis
Open accessAbstract
Over the last 20 years there has been an increasing interest in the influence of the gastrointestinal tract on appetite regulation. Much of the focus has been on the neuronal and hormonal relationship between the gastrointestinal tract and the brain. There is now mounting evidence that the colonic microbiota and their metabolic activity have a significant role in energy homeostasis. The supply of substrate to the colonic microbiota has a major impact on the microbial population and the metabolites they produce, particularly short chain fatty acids (SCFAs). SCFAs are produced when non-digestible carbohydrates, namely dietary fibres and resistant starch, undergo fermentation by the colonic microbiota. Both the consumption of fermentable carbohydrates and the administration of SCFAs have been reported to result in a wide range of health benefits including improvements in body composition, glucose homeostasis, blood lipid profiles and reduced body weight and colon cancer risk. However, published studies tend to report the effects that fermentable carbohydrates and SCFAs have on specific tissues and metabolic processes, and fail to explain how these local effects translate into systemic effects and the mitigation of disease risk. Moreover, studies tend to investigate SCFAs collectively and neglect to report the effects associated with individual SCFAs. Here, we bring together the recent evidence and suggest an overarching model for the effects of SCFAs on one of their beneficial aspects: appetite regulation and energy homeostasis.
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Probiotics may improve insulin resistance by increasing SCFA production, activating G protein-coupled receptors FFAR2 and FFAR3 on gut enteroendocrine L cells, reducing inflammatory factors, and increasing glucagon-like peptide-1 release.
“A possible mechanism is that probiotics increase the production of SCFA, which activate G protein-coupled receptors (FFAR2 and FFAR3) on gut enteroendocrine L cells. This leads to a reduction in inflammatory factors, an increase in glucagon-like peptide-1 release, and an improvement in insulin resistance(Byrne et al., 2015; Drucker, 2018).”
From Impact of probiotics on weight loss, glucose and lipid metabolism in overweight or obese women: A meta-analysis of randomized controlled trials (2024) · cites this paper as Byrne et al., 2015
The sections on SCFA receptor signalling and energy intake in animal models (page not specified) describe SCFA activation of FFA2/FFA3 and evidence that SCFAs stimulate GLP-1 release from enteroendocrine L cells. The cited passages do not establish that probiotics increase SCFA production or that this pathway reduces inflammatory factors and thereby improves insulin resistance; the paper discusses glucose-related benefits through other mechanisms. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMost short-chain fatty acids indirectly impact host metabolism by functioning as signaling molecules, for example as inhibitors of histone deacetylases or ligands for G-protein-coupled receptors, in pathways that modulate functions ranging from inflammation to energy homeostasis.
“Most SCFAs indirectly impact on host metabolism by functioning as signaling molecules, e.g., as inhibitors for histone deacetylases or ligands for G-protein-coupled receptors, in pathways that modulate functions ranging from inflammation to energy homeostasis [91,92,93].”
SCFAs (acetic acid, propionic acid, butyric acid) are fermentation end-products of non-digested carbohydrates in the colon and have been suggested to have health benefits related to weight control, lipid profiles, and colon health.
“Short-chain fatty acids (SCFAs) as acetic acid (AA), propionic acid (PPA), and butyric acid (BA), are the fermatation end-products of non-digested carbohydrates in the colon and have been suggested to have various health benefits to the host related to weight control, lipid profiles, and colon health [174].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [174]
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“This leads to a reduction in inflammatory factors, an increase in glucagon-like peptide-1 release, and an improvement in insulin resistance(Byrne et al., 2015; Drucker, 2018).”
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Self-citation
- Authors
- Byrne, C. S., Chambers, E. S., Morrison, D. J., & Frost, G.
- Affiliations
- Imperial College London (GB)
- Scottish Universities Environmental Research Centre (GB)
- Corresponding author
- Frost, G
- Venue
- International Journal of Obesity
- Published
- 2015-05-14
- Volume
- 39
- Issue
- 9
- Pages
- 1331-1338
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- PMC
- PMC4564526
- OpenAlex
- W281347911
- Cited by
- 707
- References
- 123
- Citations by year
- 2026: 49 · 2025: 73 · 2024: 71 · 2023: 62 · 2022: 79 · 2021: 88 · 2020: 80 · 2019: 61 · 2018: 52 · 2017: 48 · 2016: 38 · 2015: 4
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Obesity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Funders
- National Institute for Health and Care Research (FP7-HEALTH-2009-241592)
- Imperial College London
- Medical Research Council (FP7-HEALTH-2009-241592)
- Biotechnology and Biological Sciences Research Council (BB/L004259/1, BB/H004971/1, BB/H004815/1, FP7-HEALTH-2009-241592)
- NIHR Imperial Biomedical Research Centre
- FP7 Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Keywords
- short-chain fatty acids, appetite regulation, energy homeostasis, colonic microbiota, dietary fiber, resistant starch, fermentable carbohydrates, gut-brain axis, glucose homeostasis, lipid profile, body weight, colon cancer risk, body composition
- MeSH terms
- Appetite Regulation, Dietary Fiber, Energy Metabolism, Fatty Acids, Volatile, Fermentation, Homeostasis, Humans, Intestinal Absorption, Obesity, Evidence-Based Medicine, Gastrointestinal Tract, Host-Pathogen Interactions, Microbiota
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